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Overexpression of TTRAP inhibits cell growth and induces apoptosis in osteosarcoma cells

Caihong Zhou1, Qi Shen, Jinglun Xue

  • 1State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China.

BMB Reports
|February 26, 2013
PubMed

Insights

Overexpressing the TTRAP protein significantly inhibited osteosarcoma cell growth and triggered apoptosis. Mutations affecting TTRAP

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • TTRAP is a multi-functional protein implicated in crucial cellular processes.
  • Its specific roles in osteosarcoma tumorigenesis require further elucidation.

Purpose of the Study:

  • To investigate the effect of TTRAP overexpression on osteosarcoma cell behavior.
  • To explore the functional significance of TTRAP's tyrosyl-DNA phosphodiesterase activity in cancer.

Main Methods:

  • Lentivirus-mediated gene delivery for TTRAP overexpression in U2OS and Saos-2 cells.
  • Assessment of cell proliferation, colony formation, apoptosis, and cell cycle progression.
  • Analysis of caspase-3/-7 activity and cyclin B1 expression.
  • Utilized site-directed mutagenesis to evaluate TTRAP's enzymatic activity.

Main Results:

  • Ectopic TTRAP expression significantly suppressed osteosarcoma cell growth and colony formation.
  • TTRAP overexpression induced apoptosis in U2OS cells and G2/M cell cycle arrest in Saos-2 cells.
  • Mutations in TTRAP's tyrosyl-DNA phosphodiesterase domain, specifically TTRAP(E152A), diminished its growth-inhibitory effects.

Conclusions:

  • TTRAP acts as a suppressor of osteosarcoma cell proliferation and survival.
  • The tyrosyl-DNA phosphodiesterase activity of TTRAP is critical for its anti-proliferative function.
  • These findings contribute to understanding TTRAP's role in cancer regulation and offer potential therapeutic insights.

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